This invention is directed to the acylation of aminosulfonic acids in which the neutralization and acylation of the acid is conducted in the solid phase. Non-gas phase bimolecular reactions generally do not readily occur unless conducted in the condensed phase, e.g. in a solvent or in the molten state. This condition, whether for homogeneous or heterogeneous reactions, is generally essential for the requisite intimate physical and chemical interactions of the reactants. In the present invention, two discrete, sequential chemical reactions occur in the solid phase, i.e. (1) the neutralization step of the sulfonic acid moiety with a base and (2) the subsequent amine acylation, to produce a superior acyl-aminosulfonic acid at a reduced cost. Both essential chemical steps occur virtually quantitatively in the solid phase.
This invention is directed to acylating aminosulfonic acids, in particular the acetylation of aminosulfonic acids with acetic anhydride. The invention has substantial advantages over prior art methods because the prior art involves doing the acylation usually in the homogeneous phase in a solvent, typically water.
There are numerous prior art references to the acetylation of various aminosulfonic acids in water. For example, sulfanilic acid has been acetylated with acetic anhydride in aqueous solution after prior neutralization with potassium carbonate (Berichte, 58, 2286). German patent No. 129,000 also teaches the acetylation of sulfanilic acid and a variety of other phenyl and naphthyl aminosulfonic acids in a similar fashion. A similar industrial process is described in the BIOS Final Report 1149, p. 125 for the manufacture of acetyl sulfanilic acid. Zincke et al (Berichte, 46, 755) and German patent No. 410364 describe the acetylation of metanilic acid with acetic anhydride after neutralization in homogeneous aqueous solution, and Bucherer et al describe the substantially equivalent acetylation of 1-naphthylamino-4-sulfonic acid (J.Prakt Chem. 80, 201). The resulting acetylated materials, however, are generally very soluble in water and isolation requires salting out with substantial quantities of an inorganic salt such as sodium, potassium, or ammonium sulfate or chloride. These procedures result in reduced yield because of solubility losses, and also result in contamination of the product with salts. Other costly methods, such as spray drying, or energy intensive methods, such as evaporating to dryness, have been utilized to separate the product from the aqueous solvent.
Other workers have avoided the problems associated with the aqueous acetylation of aminosulfonic acids by employing a non-aqueous solvent, such as acetic acid or pyridine. German patent Nos.69555, 75084 and 116922 describe acetylations in acetic acid with sodium acetate as base while Kloetzel et al (J.Org. Chem., 26, 607) describe the use of acetic acid as solvent with pyridine as base. A number of works have utilized pyridine as solvent and base for the acetylation of aminosulfonic acids with acetic anhydride (A. Barco et al, Synthesis, 877 (1974); Forster et al, J. Soc.Chem. Indust., 46. 225c, and 47, 156T; Cross et al, J. Soc. Dyers Col., 59, 143 and 147). Even the use of non-aqueous solvents, however, still requires the separation of the bulk of the solvent from the product by filtration.
Some workers have utilized the neutralized, isolated salt, such as an alkali metal or heavy metal salt, of the aminosulfonic acid as the starting material and conducted the acylation, especially acetylation, in excess acetic anhydride (Nietzki et al, Berichte 17, 707; Gnelm et al, J. Prakt. Chem., 63, 405; and Schroefer, Berichte, 39, 1559). However, this has the disadvantage of introducing an additional step in the process, i.e., the isolation of the salt after base neutralization. Furthermore, these publications teach that a solvent, such as water, alcohol, or ether, or combinations of these, are required in the isolation of the acetylated products, again necessitating solvent removal.
The above prior art requires that the solvent-wet product be dried in yet another separate operation. Drying is essential, especially with water-wet products, since wet material is incompatible in the important chemical application of these materials, namely, conversion of the sulfonic acid group to the sulfochloride group with chlorosulfonic acid and/or thionyl chloride or similar reagent.
The present invention eliminates the solvent, salting out, filtration, and drying operation, and thereby substantially increases the process yield at a reduced cost. Importantly, in this age of environmental concern virtually all discharge of waste water or other liquid wastes is eliminated. The present invention directly produces a dry product in high purity and in very nearly quantitative yield. Furthermore, the process described herein is faster, more efficient and has higher space-time yields than prior technology.